The satiety factor oleoylethanolamide impacts hepatic lipid and glucose metabolism in goldfish

Abstract

Oleoylethanolamide (OEA) is an acylethanolamide synthesized mainly in the gastrointestinal tract with known effects in mammals on food intake and body mass through activation of peroxisome proliferator-activated receptor type α (PPARα). Since we previously demonstrated that acute treatment with OEA in goldfish resulted in decreased food intake and locomotor activity, as in mammals, we hypothesize that OEA would be involved in the control of energy metabolism in fish. Therefore, we assessed the effects of acute (for 6 h) and chronic (for 11 days) treatments with OEA (5 µg g body mass) on metabolite concentrations and enzyme activities related to glucose and lipid metabolism in liver of goldfish (Carassius auratus). In the chronic treatment, OEA impairs the increase in body mass and reduces locomotor activity, without any signs of stress. The lipolytic capacity in liver decreased after both acute and chronic OEA treatments, whereas lipogenic capacity increased after acute and decreased after chronic treatment with OEA. These results are different from those observed to date in mammalian adipose tissue, but not so different from those known in liver, and might be attributed to the absence of changes in the expression of pparα, and/or to the increase in the expression of the clock gene bmal1a after chronic OEA treatment. As for glucose metabolism, a clear decrease in the capacity of hepatic tissue to use glucose was observed in OEA-treated fish. These results support an important role for OEA in the regulation of liver lipid and glucose metabolism, and could relate to the metabolic changes associated with circadian activity and the regulation of food intake in fish.

Diurnal Profiles of N-Acylethanolamines in Goldfish Brain and Gastrointestinal Tract: Possible Role of Feeding

“…Thus, PPARα is considered an output gene and shows daily rhythmic expression in a variety of tissues in mammals (Yang et al, 2006; Chen et al, 2010). This interaction between OEA and the circadian system has also been suggested in fish, since hepatic expression of bmal1a increases after OEA treatment in goldfish (Gómez-Boronat et al, 2016) and the expression of pparα is rhythmic in gilthead sea bream ( Sparus auratus ; Paredes et al, 2014) and zebrafish ( Danio rerio ; Paredes et al, 2015). Apart from these data, there is no evidence in fish on the possible daily rhythmicity in OEA and other NAEs.…”

“…In fact, it has been demonstrated in mammals that PPARα stimulates fatty acid oxidation and lipid catabolism (Charoensuksai and Xu, 2010; Chen and Yang, 2014; Liu et al, 2014). In addition, bmal1a is also rhythmic increasing after feeding, supporting its role as a lipogenic factor in mammals (Shimba et al, 2005, 2011; Zhang et al, 2014), and also in goldfish (Gómez-Boronat et al, 2016). Moreover, PPARα has been largely proposed as a link between lipid metabolism and circadian system in mammals (Yang et al, 2006; Chen and Yang, 2014; Ribas-Latre and Eckel-Mahan, 2016), in which circadian rhythms of PPARα are essential for the temporal coordination of genes involved in energy and metabolic process (Charoensuksai and Xu, 2010; Chen and Yang, 2014; Ribas-Latre and Eckel-Mahan, 2016).…”

“…The most studied NAE in mammals is OEA, which acts as an anorexigenic signal and promotes fat catabolism (Bowen et al, 2017; Sihag and Jones, 2018). In goldfish, OEA also reduces food intake and body weight, and is involved in lipid and glucose metabolism (Tinoco et al, 2014; Gómez-Boronat et al, 2016). A food intake decrease was also observed after exogenous administration of PEA or SEA in the only vertebrates studied to date, rats and mice (Rodríguez de Fonseca et al, 2001; Terrazzino et al, 2004).…”

The effects of oleoylethanolamide, an endogenous PPAR‐α agonist, on risk factors for NAFLD: A systematic review

“…OEA plays a pivotal role in lipid metabolism by modulating lipids in circulation and tissues in addition to its satietogenic effect . Several experimental studies have shown the useful effects of OEA on lipid profiles (Supplemental Table 1) . Further investigations have indicated that the lipolytic activity of OEA and its effects on fatty acid mobilization by activating PPAR‐α and PPAR‐α target genes contribute to lipid metabolism .…”

Central regulation of food intake in fish: an evolutionary perspective

“…Finally, some GI fatty acid ethanolamines, structural analogues of the endocannabinoids, as oleoylethanolamide (OEA) induces satiety in mammals (Fu et al 2003) and goldfish (Tinoco et al 2014b), where it is involved in the regulation of liver lipid and glucose metabolism (Gómez-Boronat et al 2016). In the rat, OEA modulates feeding by prolonging the time interval between meals rather than meal size (Gaetani et al 2003).…”